Pharmacology-GH & PRL Disorders Flashcards
Direct effects of GH
Initiates fat metabolism and gluconeogenesis in the liver. Also stimulates IGF-1 by binding GH receptors on chondrocytes, liver, etc.
Effects of IGF-1
Increased amino acid transport into tissues, increased protein synthesis and elongation of bone
What does GHRH do?
Binds GHRH-R, activates Gs -> Adenylate cyclase -> cAMP activates PKA -> activates somatotroph GH production. GH is then released from anterior pituitary.
What does somatostatin do?
Binds SST-R. Activates Gi -> inhibits adenylate cyclase. Activates Go -> turns off Ca channel. Inhibits somatotroph production of GH in anterior pituitary.
Aside of GHRH and SST, what other things can activate growth hormone?
Hypoglycemia, amino acids, deep sleep, exercise and dopamine agonists (except for in acromegaly, DA inhibits GH in this condition)
What is the cell signaling pathway by which GH increases cellular transcription of IGF-1 and gluconeogenesis enzymes?
JAK/STAT kinase pathway
How can you test for growth hormone function in a stunted child?
Inject insulin to induce a hypoglycemic state. If the HPA is intact, GH levels will rise.
Recombinant hGH analogue
Somatropin
What other blood values do you want to know if you are starting a child with hypopituitary dwarfism on hGH?
T3 and T4 levels must be adequate for somatropin to work.
What causes Laron syndrome?
Hypersomatotrophic dwarfism is characterized by high levels of GH but defective GH receptors and inability to synthesize and release IGF-1.
Synthetic IGF-1 used to treat Laron syndrome
Mecasermin
A man comes to see you with a broad nose, elongated mandible, narrowed joints, carpal tunnel syndrome. glucose intolerance, hypertension and organ hypertrophy. What is causing his condition?
Acromegaly is caused by inactivation of the Gs GTPase and Gs/adenylyl cyclase are constitutively active despite absence of GHRF
A man comes to see you with a broad nose, elongated mandible, narrowed joints, carpal tunnel syndrome. glucose intolerance, hypertension and organ hypertrophy. Labs show hyperprolactinemia. How do you treat this patient?
Dopamine analogue bromocriptine binds D2 receptors on somatotrophs and reverts them to stem cell-like cells in 50% of acromegaly cases.
GH receptor antagonist for GH-secreting adenoma
Pegvisomant. Differs slightly from GH and complexed with polyethylene glycol
Long-acting somatostatin analogue for GH-secreting adenoma
Octreotide (lanreotide)
What happens to an at term pregnant woman if her dopamine levels really drop?
Prolactin levels will increase because DA normally inhibits lactotrophs by blocking Ca channels and adenylate cyclase. She will be at increased chance of parturition.
How does the hypothalamus initiate increased levels of prolacting?
It releases TRH (thyroid releasing hormone). TRH binds lactotrophs, activates Gq -> PLC. PIP2 is converted to IP3, intracellular Ca levels rise and increased levels of prolactin are synthesized.
Causes of hyperprolactinemia
Lack of sufficient DA, adenoma of lactotrophs, hypothyroidism (excess TRH stimulates lactotrophs) and antipsychotic drugs (block D2 receptors)
Symptoms of hyperprolactinemia
Galactorrhea, gynecomastia, amenorrhea and loss of vision (compression of optic nerve)
Why is hyperprolactinemia a common cause of infertility?
Elevated prolactin decreases GnRH levels and causes reversible infertility
Treatment of hyperprolactinemia
Surgery, bromocriptine (D2 agonist causes adenoma to shrink)
Why is cabergoline almost perfect for treating hyperprolactinemia?
In addition to activating D2 receptors, it activates 5HT2B receptors that causes proliferation of the mitral valve.
When do you use bromocriptine in pregnancy?
Usually only if its a macro adenoma
